Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis
01 Mar 2013-Bulletin of The World Health Organization (World Health Organization)-Vol. 91, Iss: 3, pp 217-226
TL;DR: Untreated maternal syphilis is associated with adverse pregnancy outcomes and these findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women.
Abstract: OBJECTIVE: To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. METHODS: PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. FINDINGS: Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0-74.1]; I(2) = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; I(2) = 95.9%; P < 0.001). CONCLUSION: Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women.
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TL;DR: A Perspective discussing the factors that have contributed to the success and failure of point-of-care tests for resource-limited settings and the challenges and opportunities that exist for developing new infectious disease diagnostics.
Abstract: Copyright: 2018. Due to copyright restrictions, the attached PDF file only contains the abstract version of the full-text item. For access to the full-text item, please consult the publisher's website. The definitive version of the work is published in Nature Microbiology, vol 4, pp. 46-54
336 citations
TL;DR: Using multinational surveillance data, Lori Newman and colleagues estimate global rates of active syphilis in pregnant women, adverse effects, and antenatal coverage and treatment needed to meet WHO goals.
Abstract: Background
The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥90% of pregnant women to be tested for syphilis and ≥90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis.
Methods and Findings
Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was “probable active,” and for testing and treatment coverage.
Conclusions
Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed.
330 citations
04 Dec 2014
TL;DR: The sexual and reproductive health care that women need and use over the course of their lives is looked at and gaps in services that if filled could improve their health as well as that of their partners and children are identified.
Abstract: To help decision-makers evaluate the investments needed in developing countries this report provides new estimates for 2014 of the needs for and costs and benefits of sexual and reproductive health interventions in three key areas: Contraceptive services; Maternal newborn and other pregnancy-related care; Selected services related to HIV and other STIs for women of reproductive age. The report shows the immediate and direct benefits of investing in each set of interventions individually and the additional benefits of investing in them all simultaneously as well as the cost implications of the investments. It also summarizes important findings from other studies that have quantified the broad long-term benefits of these investments for individuals and societies. This report focuses in particular on the populations with the greatest needs for services to highlight those who are most vulnerable and dependent on public-sector care and subsidies. Assessing the differences among population subgroups countries and geographic regions can help guide national governments and international agencies in allocating resources and making other program decisions that would help to close existing gaps in services. The report does not examine men’s sexual and reproductive health needs independently from those of women although men’s needs are critical to address in their own right. Rather this report looks at the sexual and reproductive health care that women need and use over the course of their lives and identifies gaps in services that if filled could improve their health as well as that of their partners and children. A large body of research shows that when women and their children survive and thrive their families are on surer financial footing and gains can also be seen in education employment and the economy. (Excerpt)
246 citations
TL;DR: Achieving global CS elimination will require improving access to early syphilis screening and treatment in ANC, clinically monitoring all women diagnosed with syphilis and their infants, improving partner management, and reducing syphilis prevalence in the general population by expanding testing, treatment and partner referral beyond ANC.
Abstract: Background In 2007 the World Health Organization (WHO) launched the global initiative to eliminate mother-to-child transmission of syphilis (congenital syphilis, or CS). To assess progress towards the goal of <50 CS cases per 100,000 live births, we generated regional and global estimates of maternal and congenital syphilis for 2016 and updated the 2012 estimates. Methods Maternal syphilis estimates were generated using the Spectrum-STI model, fitted to sentinel surveys and routine testing of pregnant women during antenatal care (ANC) and other representative population data. Global and regional estimates of CS used the same approach as previous WHO estimates. Results The estimated global maternal syphilis prevalence in 2016 was 0.69% (95% confidence interval: 0.57–0.81%) resulting in a global CS rate of 473 (385–561) per 100,000 live births and 661,000 (538,000–784,000) total CS cases, including 355,000 (290,000–419,000) adverse birth outcomes (ABO) and 306,000 (249,000–363,000) non-clinical CS cases (infants without clinical signs born to un-treated mothers). The ABOs included 143,000 early fetal deaths and stillbirths, 61,000 neonatal deaths, 41,000 preterm or low-birth weight births, and 109,000 infants with clinical CS. Of these ABOs– 203,000 (57%) occurred in pregnant women attending ANC but not screened for syphilis; 74,000 (21%) in mothers not enrolled in ANC, 55,000 (16%) in mothers screened but not treated, and 23,000 (6%) in mothers enrolled, screened and treated. The revised 2012 estimates were 0.70% (95% CI: 0.63–0.77%) maternal prevalence, and 748,000 CS cases (539 per 100,000 live births) including 397,000 (361,000–432,000) ABOs. The estimated decrease in CS case rates between 2012 and 2016 reflected increased access to ANC and to syphilis screening and treatment. Conclusions Congenital syphilis decreased worldwide between 2012 and 2016, although maternal prevalence was stable. Achieving global CS elimination, however, will require improving access to early syphilis screening and treatment in ANC, clinically monitoring all women diagnosed with syphilis and their infants, improving partner management, and reducing syphilis prevalence in the general population by expanding testing, treatment and partner referral beyond ANC.
214 citations
TL;DR: Evidence defining treatment for HIV-infected persons and for pregnant women is limited, but available data support penicillin as first-line therapy, despite the relatively modest clinical trial data that support its use.
Abstract: Importance The incidence of syphilis in the United States is increasing; it is estimated that more than 55 000 new infections will occur in 2014. Treatment regimens are controversial, especially in specific populations, and assessing treatment response based on serology remains a challenge. Objective To review evidence regarding penicillin and nonpenicillin regimens, implications of the “serofast state,” and treatment of specific populations including those with neurosyphilis or human immunodeficiency virus (HIV) infection and pregnant women. Evidence Review We searched MEDLINE for English-language human treatment studies dating from January 1965 until July 2014. The American Heart Association classification system was used to rate quality of evidence. Findings We included 102 articles in our review, consisting of randomized trials, meta-analyses, and cohort studies. Case reports and small series were excluded unless they were the only studies providing evidence for a specific treatment strategy. We included 11 randomized trials. Evidence regarding penicillin and nonpenicillin regimens was reviewed from studies involving 11 102 patients. Data on the treatment of early syphilis support the use of a single intramuscular injection of 2.4 million U of benzathine penicillin G, with studies reporting 90% to 100% treatment success rates. The value of multiple-dose treatment of early syphilis is uncertain, especially in HIV-infected individuals. Less evidence is available regarding therapy for late and late latent syphilis. Following treatment, nontreponemal serologic titers should decline in a stable pattern, but a significant proportion of patients may remain seropositive (the “serofast state”). Serologic response to treatment should be evident by 6 months in early syphilis but is generally slower (12-24 months) for latent syphilis. Evidence defining treatment for HIV-infected persons and for pregnant women is limited, but available data support penicillin as first-line therapy. Conclusions and Relevance The mainstay of syphilis treatment is parenteral penicillin G despite the relatively modest clinical trial data that support its use.
183 citations
Cites background from "Untreated maternal syphilis and adv..."
...65 However, in some settings, penicillin is clearly the treatment of choice and desensitization is probably the preferred option in the following situations: (1) neurosyphilis in persons with a history of severe immediate hypersensitivity reaction to penicillin; (2) tertiary syphilis in all penicillin-allergic patients; (3) any stage of syphilis in penicillin-allergic pregnant women; and (4) congenital syphilis in penicillin-allergic infants....
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References
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TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
62,157 citations
Journal Article•
TL;DR: The QUOROM Statement (QUality Of Reporting Of Meta-analyses) as mentioned in this paper was developed to address the suboptimal reporting of systematic reviews and meta-analysis of randomized controlled trials.
Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews.
Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7
In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1).
Box 1
Conceptual issues in the evolution from QUOROM to PRISMA
46,935 citations
TL;DR: A structured summary is provided including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings.
31,379 citations
TL;DR: A checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion should improve the usefulness ofMeta-an analyses for authors, reviewers, editors, readers, and decision makers.
Abstract: ObjectiveBecause of the pressure for timely, informed decisions in public health
and clinical practice and the explosion of information in the scientific literature,
research results must be synthesized. Meta-analyses are increasingly used
to address this problem, and they often evaluate observational studies. A
workshop was held in Atlanta, Ga, in April 1997, to examine the reporting
of meta-analyses of observational studies and to make recommendations to aid
authors, reviewers, editors, and readers.ParticipantsTwenty-seven participants were selected by a steering committee, based
on expertise in clinical practice, trials, statistics, epidemiology, social
sciences, and biomedical editing. Deliberations of the workshop were open
to other interested scientists. Funding for this activity was provided by
the Centers for Disease Control and Prevention.EvidenceWe conducted a systematic review of the published literature on the
conduct and reporting of meta-analyses in observational studies using MEDLINE,
Educational Research Information Center (ERIC), PsycLIT, and the Current Index
to Statistics. We also examined reference lists of the 32 studies retrieved
and contacted experts in the field. Participants were assigned to small-group
discussions on the subjects of bias, searching and abstracting, heterogeneity,
study categorization, and statistical methods.Consensus ProcessFrom the material presented at the workshop, the authors developed a
checklist summarizing recommendations for reporting meta-analyses of observational
studies. The checklist and supporting evidence were circulated to all conference
attendees and additional experts. All suggestions for revisions were addressed.ConclusionsThe proposed checklist contains specifications for reporting of meta-analyses
of observational studies in epidemiology, including background, search strategy,
methods, results, discussion, and conclusion. Use of the checklist should
improve the usefulness of meta-analyses for authors, reviewers, editors, readers,
and decision makers. An evaluation plan is suggested and research areas are
explored.
17,663 citations
Book•
30 Nov 2000
TL;DR: The second edition of this best-selling book has been thoroughly revised and expanded to reflect the significant changes and advances made in systematic reviewing.
Abstract: The second edition of this best-selling book has been thoroughly revised and expanded to reflect the significant changes and advances made in systematic reviewing. New features include discussion on the rationale, meta-analyses of prognostic and diagnostic studies and software, and the use of systematic reviews in practice.
2,601 citations